Childrens Hospital of Michigan

Detroit, MI, United States

Childrens Hospital of Michigan

Detroit, MI, United States

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Vangipuram S.D.,Childrens Hospital of Michigan | Lyman W.D.,Childrens Hospital of Michigan
Alcoholism: Clinical and Experimental Research | Year: 2010

Background: Prenatal ethanol (ETOH) exposure can lead to fetal alcohol spectrum disorder (FASD). We previously showed that ETOH alters cell adhesion molecule gene expression and increases neurosphere size in fetal brain-derived neural stem cells (NSC). Here, our aim was to determine the effect of ETOH on the cell fate of NSC, premature glial-committed precursor cells (GCP), and premature neuron-committed progenitor cells (NCP). Methods: NSC, GCP, and NCP were isolated from normal second-trimester fetal human brains (n = 3) by positive selection using magnetic microbeads labeled with antibodies to CD133 (NSC), A2B5 (GCP), or PSA-NCAM (NCP). As a result of the small percentage in each brain, NSC were cultured in mitogenic media for 72 hours to produce neurospheres. The neurospheres from NSC and primary isolates of GCP and NCP were used for all experiments. Equal numbers of the 3 cell types were treated either with mitogenic media or with differentiating media, each containing 0 or 100 mM ETOH, for 120 hours. Expression of Map2a, GFAP, and O4 was determined by immunoflourescence microscopy and western blot analysis. Fluorescence intensities were quantified using Metamorph software by Molecular Devices, and the bands of western blots were quantified using densitometry. Results: ETOH in mitogenic media promoted formation of neurospheres by NSC, GCP, and NCP. Under control conditions, GCP attached and differentiated, NSC and NCP formed neurospheres that were significantly smaller in size than those in ETOH. Under differentiating conditions, Map2a expression increased significantly in NSC and GCP and reduced significantly in NCP, and GFAP expression reduced significantly in GCP and NCP, and Gal-C expression reduced significantly in all 3 cell types in the presence of ETOH compared to controls. Conclusions: This study shows that ETOH alters the cell fate of neuronal stem and progenitor cells. These alterations could contribute to the mechanism for the abnormal brain development in FASD. © 2010 by the Research Society on Alcoholism.


Linet M.S.,U.S. National Cancer Institute | Slovis T.L.,Childrens Hospital of Michigan | Miller D.L.,U.S. Food and Drug Administration | Kleinerman R.,U.S. National Cancer Institute | And 3 more authors.
CA Cancer Journal for Clinicians | Year: 2012

The 600% increase in medical radiation exposure to the US population since 1980 has provided immense benefit, but increased potential future cancer risks to patients. Most of the increase is from diagnostic radiologic procedures. The objectives of this review are to summarize epidemiologic data on cancer risks associated with diagnostic procedures, describe how exposures from recent diagnostic procedures relate to radiation levels linked with cancer occurrence, and propose a framework of strategies to reduce radiation from diagnostic imaging in patients. We briefly review radiation dose definitions, mechanisms of radiation carcinogenesis, key epidemiologic studies of medical and other radiation sources and cancer risks, and dose trends from diagnostic procedures. We describe cancer risks from experimental studies, future projected risks from current imaging procedures, and the potential for higher risks in genetically susceptible populations. To reduce future projected cancers from diagnostic procedures, we advocate the widespread use of evidence-based appropriateness criteria for decisions about imaging procedures; oversight of equipment to deliver reliably the minimum radiation required to attain clinical objectives; development of electronic lifetime records of imaging procedures for patients and their physicians; and commitment by medical training programs, professional societies, and radiation protection organizations to educate all stakeholders in reducing radiation from diagnostic procedures. Copyright © 2012 American Cancer Society, Inc.


Veire A.,Childrens Hospital of Michigan
The Journal of the Michigan Dental Association | Year: 2012

Management of dental trauma in children can be a challenging problem in dental practices. Knowledge of current trauma guidelines is vital in effectively managing dental trauma so that favorable outcomes are achieved. The purpose of this paper is to review the current guidelines and management strategies of dental trauma in primary and permanent dentitions. When planning emergency treatment for a primary tooth, it is important to consider the lifespan of the tooth, the potential damage to the permanent dentition, and the behavior of the child. After injury to permanent teeth, the treatment strategy is dictated by the concern for vitality of the periodontal ligament and pulp of the injured tooth. The emergency nature of dental trauma requires that the dentist be knowledgeable and readily available during and after office hours to provide care.


Qawasmi A.,Yale University | Qawasmi A.,Childrens Hospital of Michigan | Landeros-Weisenberger A.,Yale University | Bloch M.H.,Yale University
Pediatrics | Year: 2013

BACKGROUND AND OBJECTIVE: Long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to affect visual acuity development in infants. Randomized controlled trials (RCTs) have been conducted to assess whether supplementation of LCPUFAs of infant formulas affects infant visual acuity. This meta-analysis was conducted to evaluate whether LCPUFA supplementation of infant formulas improves infants' visual acuity. METHODS: PubMed and PsycInfo were searched for RCTs assessing the efficacy of LCPUFA supplementation of infant formulas on infant visual acuity. RCTs assessing the effects of LCPUFA supplementation on visual acuity (by using either visual evoked potential or behavioral methods) in the first year of life were included in this meta-analysis. Our primary outcome was the mean difference in visual resolution acuity (measured in logarithm of minimum angle of resolution [logMAR]) between supplemented and unsupplemented infants. We also conducted secondary subgroup analyses and meta-regression examining the effects of LCPUFA dose and timing, preterm versus term birth status, and trial methodologic quality. RESULTS: Nineteen studies involving 1949 infants were included. We demonstrated a significant benefit of LCPUFA supplementation on infants' visual acuity at 2, 4, and 12 months of age when visual acuity was assessed by using visual evoked potential and at 2 months of age by using behavioral methods. There was significant heterogeneity between trials but no evidence of publication bias. Secondary analysis failed to show any moderating effects on the association between LCPUFA supplementation and visual acuity. CONCLUSIONS: Current evidence suggests that LCPUFA supplementation of infant formulas improves infants' visual acuity up to 12 months of age. Copyright © 2013 by the American Academy of Pediatrics.


Chitlur M.,Childrens Hospital of Michigan
Thrombosis Research | Year: 2012

Standard coagulation assays such as the activated partial thromboplastin time and prothrombin time are sufficient to detect deficiencies in coagulation factors contributing to the intrinsic and extrinsic pathways, respectively. Deficiencies in factors VIII and IX can also be detected by one-stage and two-stage clotting assays. While these assays are instrumental in assessing the initiation of clot formation, sufficient formation of a clot is a continuous process that may be better studied by the use of a global hemostasis assay. Several global assays are currently being studied, including the thrombin generation assay, thromboelastography, clot waveform analysis, clot formation and lysis (CloFAL) assay, euglobulin clot lysis assay, thromboplastin generation assays and simultaneous thrombin and plasmin generation assays. This review will concentrate on the thrombin generation test, thromboelastography, the activated partial thromboplastin time waveform analysis and the CloFAL which measure the production of thrombin, as well as the kinetics of clot formation. As such, these global assays can provide greater insight into deficiencies in the mechanisms mediating hemostasis and fibrinolysis in patients with hemophilia, other bleeding disorders or even thrombophilia. These assays have been shown to be clinically relevant for assessing the response to treatment with bypassing agents (recombinant activated FVII and plasma-derived prothrombin complex concentrate) used for the hemostatic control of acute bleeding in patients with congenital hemophilia A/B. The limitations of standard coagulation assays and the use of global hemostasis assays to assess bleeding disorders and the clinical efficacy of bypassing agents will be discussed in detail. © 2012 Elsevier Ltd. All rights reserved.


Slovis T.L.,Childrens Hospital of Michigan
Pediatric radiology | Year: 2011

In the last decade, there has been recognition of the effects of low-dose radiation in children. A critical mass of scientists, health care providers and manufacturers of radiation-producing imaging equipment has come together to educate ordering physicians to request only indicated examinations and radiologists to achieve low-dose examinations with diagnostic images. The forces that caused these changes will be discussed.


Slovis T.L.,Childrens Hospital of Michigan
Pediatric radiology | Year: 2011

Sedation and anesthesia for pediatric imaging departments has changed dramatically for the following reasons: (1) radiologists have stopped sedating patients; (2) the majority of sedations are not for CT (because of the speed of the procedure) but for MR, which lasts 45 min or greater; (3) a cadre of services--pediatricians, emergency medicine physicians, hospitalists and intensivists, as well as anesthesiologists--can provide the services. These changes have significantly influenced the type of agents utilized for sedation and anesthesia and, most important, have created operational issues for MR departments. Nevertheless, it is important for each imaging department to create a uniform approach to sedation, taking into account patient expectations, efficiency of through-put, facilities and personnel available, and institutional costs.


Plant A.L.,U.S. National Institute of Standards and Technology | Parker G.C.,Childrens Hospital of Michigan
Stem Cells and Development | Year: 2013

Stem cell therapies show great medical promise, but few new products have made it into the marketplace. The translation of stem and other cell therapies faces not only challenges associated with research and development, but also the challenges of investment funding and regulatory approval. Regulators and investors alike appear to be voicing the same concerns: they see (1) insufficient high-quality data to provide confidence regarding the claims of medical benefit, (2) an insufficient understanding of the mechanism of action, and (3) a lack of identification of essential characteristics for product release criteria and for assuring reproducibility in manufacturing. The ensuing frustration on the part of researchers and developers may be the result of failure to fully comprehend what is required to assure that confidence. © Copyright 2013, Mary Ann Liebert, Inc. 2013.


Gupta N.,Childrens Hospital of Michigan | Gupta N.,Rochester College | Goel K.,Rochester College | Goel K.,Diabetes Foundation India | And 5 more authors.
Endocrine Reviews | Year: 2012

Rapidly changing dietary practices and a sedentary lifestyle have led to increasing prevalence of childhood obesity (5-19 yr) in developing countries recently: 41.8% in Mexico, 22.1% in Brazil, 22.0% in India, and 19.3% in Argentina. Moreover, secular trends indicate increasing prevalence rates in these countries: 4.1 to 13.9% in Brazil during 1974-1997, 12.2 to 15.6% in Thailand during 1991-1993, and 9.8 to 11.7% in India during 2006-2009. Important determinants of childhood obesity include high socioeconomic status, residence in metropolitan cities, female gender, unawareness and false beliefs about nutrition, marketing by transnational food companies, increasing academic stress, and poor facilities for physical activity. Childhood obesity has been associated with type 2 diabetes mellitus, the early-onset metabolic syndrome, subclinical inflammation, dyslipidemia, coronary artery diseases, and adulthood obesity. Therapeutic lifestyle changes and maintenance of regular physical activity through parental initiative and social support interventions are the most important strategies in managing childhood obesity. Also, high-risk screening and effective health educational programs are urgently needed in developing countries. © 2012 by The Endocrine Society.


Mattoo T.K.,Childrens Hospital of Michigan
Advances in Chronic Kidney Disease | Year: 2011

Primary vesicoureteral reflux (VUR) is the commonest congenital urological abnormality in children, which has been associated with an increased risk of urinary tract infection (UTI) and renal scarring, also called reflux nephropathy (RN). In children, RN is diagnosed mostly after UTI (acquired RN) or during follow-up for antenatally diagnosed hydronephrosis with no prior UTI (congenital RN). The acquired RN is more common in female children, whereas the congenital RN is more common in male children. This observation in children might help explain the differences in the clinical presentation of RN in adults, with males presenting mostly with hypertension, proteinuria, and progressive renal failure as compared with females who present mostly with recurrent UTI and have a better outcome. Known risk factors for RN include the severity of VUR, recurrent UTI, and bladder-bowel dysfunction; younger age and delay in treatment of UTI are believed to be other risk factors. Management of VUR is controversial and includes antimicrobial prophylaxis, surgical intervention, or surveillance only. No evidence-based guidelines exist for appropriate follow-up of patients with RN. © 2011 National Kidney Foundation, Inc.

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